Methods for the analysis of fluid material, e.g., industrial and biological fluids, are well known. Despite the wide variety of tests which have been developed for the determination of specific constituents in fluids, a similarity exists in the steps associated with each process. For example, a suitable sample or specimen must be acquired, which in the case of body fluids means that a suitable urine, blood, etc. specimen must be obtained from a patient. The specimen or sample must then be suitably stored and preserved if not analyzed immediately. Frequently, the specimen must be prepared by centrifugation, filtration, dilution, etc. and then reacted with appropriate chemical reagents. Ultimately, it is necessary to abstract information about the specimen or sample by transducing a chemical signal, which can be a color change, into an electronic signal which in turn can be processed and combined with other relevant data to arrive at a final assessment of a specific constituent present in the sample or specimen, thereby facilitating a clinical decision.
Conventional liquid reagent systems tend to be complicated, time consuming and expensive. In the case of optical systems a light source has to be provided, a spectral or intensity change has to occur during reagent-sample interaction, and this change must be detected and processed.
The essential steps needed for electrochemical analysis systems are reduced somewhat, but still require an amperometric probe device having a constant voltage source, a specific electrode and a current monitor.
Reagent strip test devices have enjoyed wide use in many analytical applications, especially in the chemical analysis of biological fluids, because of their relatively low cost, ease of usability and speed in obtaining results. In medicine, for example, numerous physiological functions can be monitored merely by dipping reagent strip test devices into a sample of body fluid, such as urine or blood, and observing a detectable response such as a change of color or a change in the amount of light reflected from or adsorbed by the reagent strip test device. An optical device, such as a reflectance photometer, is required in order to automate or semiautomate the analysis of reagent strip test devices.
Ideally, an analytical device and method for detecting a constituent in a sample should comprise a nonoptical sensing element which has no electrodes, requires no direct current connection, requires no membrane, is inexpensive to the point of being disposable, is specific and sensitive, is rapid in response, is easy to use and can be employed directly with an unmodified specimen.
Techniques for making quantitative chemical determinations and estimations through measurement of the change in conductivity of a test system before and after reaction of the substance to be detected with a test reagent are generally known. For example, one method for the quantitative determination of an enzyme or substrate involves the measurement of the change in electrical conductivity of the test system resulting from interaction of the enzymes and substrate. This is described in an article entitled "Conductivity Method for Determination of Urea" by W. T. Chin et al. published in Analytical Chemistry, Nov. 1961, at pages 1757-1760. This method measures the electrical conductivity in a test fluid containing urea before and after reaction with urease and thereafter requires calculations to be made of the change in conductivity.
Another method for analytically studying the elements of an enzyme-substrate reaction is disclosed in U.S. Pat. No. 3,421,982. The apparatus disclosed in U.S. Pat. No. 3,421,982 includes circuitry which requires continuous manual adjustment to obtain a measurement of the change in conductivity upon reaction of test fluid and reagent. Moreover, the method is based on the assumption that the reaction produces a linear rate of change of conductivity.
U.S. Pat. No. 3,635,681 provides differential conductivity measuring apparatus comprising a pair of probes, each of which includes a pair of spaced electrodes. Electrodes of the first probe are in intimate contact with a test reagent, such as an enzyme, incorporated within the matrix. The electrodes of the second probe are also in intimate contact with a matrix. In use, the first and second probes are contacted with an ionic medium containing the substance to be detected. The conductivity measured by the second probe is dependent upon the conductivity of the matrix means associated with the electrodes of said probe and the ionic medium and the conductivity of the first probe is dependent upon the conductivity of the ionic medium and the matrix means associated with the electrodes of the first probe, as well as upon any change in conductivity produced by a chemical reaction.
A. J. Frank and Kenji Honda, "Polypyrrole Coated Semiconductor Electrodes", J. Electrochem. Soc., 82-1:992 (1982), disclose the use of a transition metal catalyst (Ru) painted onto polymer to protect CdS and CdSe semiconductor electrodes from photocorrosion in aqueous electrolyte.
N. N. Savvin, E. E. Gutman, I. A. Myasnikov and V. P. Bazov, Kinet. Catal., 19(3):634-636 (1978), "Investigation of the Elementary Stages of the Catalytic Decomposition of Hydrogen Peroxide on Metal Oxides by Conductometric Analysis and IR Spectroscopy" have shown, on the basis of experimental data, that the primary event in the decomposition of hydrogen peroxide on metal oxides (ZnO and NiO) involves preferential rupture of the O--O bond in the H.sub.2 O.sub.2 molecule to form chemisorbed hydroxyl radicals. The superstoichiometric metal atoms in the oxides can act as active centers for the decomposition of hydrogen peroxide in the gas phase. Conductivity changes are observed in the catalyst (ZnO, NiO).
The reaction of FeCl.sub.3 dissolved in dry nitromethane with polyacetylene, (CH).sub.x, results in the formation of p-type conducting polymers (O=780 ohm.sup.-1) according to A. Pron, D. Billaud, I. Kulszewicz, C. Budrowski, J. Przyluski, and J. Suwalski, "Synthesis and Characterization of New Organic Metals Formed by Interaction of FeCl.sub.3 with Polyacetylene (CH).sub.x and Poly(para)phenylene (C.sub.6 H.sub.6).sub.x ", Mat. Res. Bull., 16: 1229-1235 (1981). IR spectra of (CH.sub.x) lightly doped with FeCl.sub.3 exhibit the formation of two new bands characteristic of other p-type dopants of (CH).sub.x. Mossbauer spectroscopy shows that the anion formed in the reaction is a high spin Fe.sup.II complex. The doping causes significant change in (CH).sub.x interchain distances as evidenced by X-ray diffraction. Similar reaction occurs between poly(para)phenylene, (C.sub.6 H.sub.4).sub.x and FeCl.sub.3 causing the increase of the conductivity of compressed poly(para)phenylene powder to metallic regime. The reaction mechanism is more complex than in the case of (CH).sub.x since Mossbauer spectroscopy shows the existence of two types of Fe.sup.II iron ions.
A quantitative theory of the electrode surface conductance decrease caused by absorbed ions is discussed by W. J. Anderson and W. N. Hansen, "Electrode Surface Conductance Measurements in an Electrochemical Cell", J. Electrochem. Soc., 121(12):1570-1575 (1974). Conductance measurements are shown to provide a reliable measure of absorbed ion surface concentration. Changes in the absorbed state are detected as a function of electrode potential. The conductance measurements are used to measure the ionic diffusion rate of I.sup.- through an aqueous electrolyte.
U.S. Pat. No. 4,334,880 describes a polyacetylene element in which the electrical characteristics of a specific binding substance, such as an antibody molecule, is used to influence the conductivity state of the polyacetylene element.
R. A. Bull, F. R. Ran, A. J. Bard, "Incorporation of Catalysts into Electronically Conductive Polymers: Iron Phthalocyanine in Polypyrrole", J. Electrochem. Soc., 130(7):1636 (1983) disclose the deposition of polymer onto a glassy carbon electrode and current voltage properties are studied in a traditional electrochemical system with opposing electrodes. No conductivity changes in the polymer are mentioned.
W. W. Harvey, "Conductance of Germanium in Contact with Aqueous Electrolytes", Am. N.Y. Acad. Sci., 101:904-914 (1963), teaches the passage of current parallel to the interface in a semiconductor contacting an electrolyte to obtain electrolytic polarization of the interphase. A portion of the longitudinal current flows in the electrolyte. Since a substantial fraction of an applied semiconductor-electrolyte potential difference falls within the space charge region of the semiconductor, the semiconductor surface potential varies with position as a consequence of the polarization attending longitudinal current flow.
U.S. Pat. No. 3,574,072 describes the electrochemical polymerization of hetrocyclic compounds, including pyrrole.